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  4. DL4-mediated Notch signaling is required for the development of fetal alpha beta and gamma delta T cells
 
research article

DL4-mediated Notch signaling is required for the development of fetal alpha beta and gamma delta T cells

Ferrero, Isabel
•
Koch, Ute  
•
Claudinot, Stephanie
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2013
European Journal of Immunology

T-cell development depends upon interactions between thymocytes and thymic epithelial cells (TECs). The engagement of delta-like 4 (DL4) on TECs by Notch1 expressed by blood-borne BM-derived precursors is essential for T-cell commitment in the adult thymus. In contrast to the adult, the earliest T-cell progenitors in the embryo originate in the fetal liver and migrate to the nonvascularized fetal thymus via chemokine signals. Within the fetal thymus, some T-cell precursors undergo programmed TCR gamma and TCR delta rearrangement and selection, giving rise to unique gamma delta T cells. Despite these fundamental differences between fetal and adult T-cell lymphopoiesis, we show here that DL4-mediated Notch signaling is essential for the development of both alpha beta and gamma delta T-cell lineages in the embryo. Deletion of the DL4 gene in fetal TECs results in an early block in alpha beta T-cell development and a dramatic reduction of all gamma delta T-cell subsets in the fetal thymus. In contrast to the adult, no dramatic deviation of T-cell precursors to alternative fates was observed in the fetal thymus in the absence of Notch signaling. Taken together, our data reveal a common requirement for DL4-mediated Notch signaling in fetal and adult thymopoiesis.

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Type
research article
DOI
10.1002/eji.201343527
Web of Science ID

WOS:000328074000028

Author(s)
Ferrero, Isabel
Koch, Ute  
Claudinot, Stephanie
Favre, Stephanie
Radtke, Freddy  
Luther, Sanjiv A.
Macdonald, H. Robson
Date Issued

2013

Publisher

Wiley

Published in
European Journal of Immunology
Volume

43

Issue

11

Start page

2845

End page

2853

Subjects

Delta-like 4

•

Fetal T-cell development

•

FoxN1Cre

•

Thymic epithelial cells

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPRAD  
Available on Infoscience
January 20, 2014
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/99996
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